This project will study the role of desmosomes in tumor cell motility and invasion in vitro. Using time lapse video microscopy, the motility of single cells as well as a sheet of cells will be studied quantitatively. The rat bladder tumor cell line NBT-II will be used in this study as it has been shown to migrate actively and to invade the human amnion in vitro. NBT-II cells will be grown in serum free defined medium, the effects of various treatment on cell migration on collagen will be compared with that on glass. A recently developed culture method, floating cultures, will be used to study cell motility in a new dimension, since in this system cells are reacting to the air/liquid interface instead of a solid substratum. This technique also allows one to examine at the light and electron microscopy level, the interaction between the basal side of cells to laminin, fibronectin and related synthetic peptides, in the absence of a solid substratum on which these molecules are usually absorbed. The effect of dimethylsulfoxide (DMSO) and calcium ions on the formation and dissolution of desmosome will be studied by using specific anti-desmosomal anti-body staining. The effect of modulating desmosomes on cell motility and cell invasion will be studied. The long term objective of this project is based on the premise that the ability of tumor cells to invade and metastasize is reflected in the mode and control of tumor cell motility and invasion in vitro. It is further postulated that the formation and dissolution of desmosomes could affect tumor cell motility and invasion. Studies on the mechanism of tumor cell invasion might lead to the development of new approaches to cancer therapy.